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PURPOSE To identify retinal genes and their relevant expression pathways affected by intravitreal injections of dexamethasone and triamcinolone acetonide in mice at clinically relevant time points for patient care. METHODS Differential gene expression of over 34,000 well-characterized mouse genes, in the retinas of 6 weeks old C57BL/6J mice were analyzed after intravitreal steroid injections at 1 week and 1 month time points, using Affymetrix Mouse Genome 430 2.0 microarrays. The data were analyzed using GeneSpringGX11 and Ingenuity Pathway Analysis (IPA) microarray analysis software for biologically relevant changes. RESULTS A common gene pathway, with differentially activated genes for both steroids and time points was ‘Semaphorin Signaling in Neurons’, a member of ‘Axonal Guidance Signaling System’. At 1 week post-injections a common theme was activation of genes expressed in retinal glial cells, TNF alpha and TGF beta signaling pathways and upregulation of stress response proteins (Serpina3n, Cebpd), as well as neuropeptide signaling somatostatin receptor (Sstr2). Unique for Dex was the upregulation of acute phase proteins (Gfap, Cp, Edn2) as well as Plexna2, a semaphorin signaling receptor, while EphrinB receptor ephexin1 (Argef15) was downregulated. Folate signaling appears to be unique for TAA at 1 week (Folh1, Cubn), while aryl-hydrocarbon receptor (AhR) signaling might be important for both steroids at 1 month. CONCLUSIONS Understanding the molecular and genetic effects of intraocular steroid treatments is of clinical relevance. This in vivo study has elucidated several genes and pathways that are potentially altering the neuroprotective/neurodegenerative balance between glial and retinal ganglion cells during intravitreal steroid treatment. Total of 18 retinal samples were analysed. There were two time points, day7 and day30. Each time point had three groups: BSS control, DEX treatment and TAA treatment. Each group had three biological replicas.